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LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
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2018 (English)In: International journal of oncology, ISSN 1791-2423, Vol. 52, no 4, p. 1189-1197Article in journal (Refereed) Published
Abstract [en]

Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.

Place, publisher, year, edition, pages
2018. Vol. 52, no 4, p. 1189-1197
Keywords [en]
thyroid cancer, LRIG1, RET, C634R, M918T, MEN2A, MEN2B
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:umu:diva-145641DOI: 10.3892/ijo.2018.4273ISI: 000427164400013PubMedID: 29436694OAI: oai:DiVA.org:umu-145641DiVA, id: diva2:1189598
Funder
Swedish Society for Medical Research (SSMF)Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2018-06-09Bibliographically approved

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Lindquist, DavidHerdenberg, CarlHenriksson, RogerHedman, Håkan

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